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PEOPLE WITH LUPUS MIGHT BE AT A GREATER RISK FOR CANCER

ATLANTA - People with systemic lupus erythematosus are 1.15 times as likely to develop cancer as the general population and more than 2.5 times as likely to develop hematologic malignancies, such as lymphoma and leukemia, according to research presented this week at the American College of Rheumatology Annual Scientific Meeting in Atlanta.

Systemic lupus erythematosus, also called SLE or lupus, is a chronic inflammatory disease that can affect the skin, joints, kidneys, lungs, nervous system, and/or other organs of the body. The most common symptoms include skin rashes and arthritis, often accompanied by fatigue and fever. Lupus occurs mostly in women, typically developing in individuals in their twenties and thirties - prime child-bearing age.

Some studies have shown a link between lupus and cancer risk, and researchers recently aimed to make more precise estimations of this risk. They observed 13,492 people with lupus from 24 medical centers for an average of nine years, for a total of 118,359 patient-years (number of patients multiplied by number of years of observation), and compared these participants to people without lupus.

During the course of this study, 632 cases of cancer were noted, and the data concerning hematological cancers—cancers that affect the bone, blood and lymph nodes—was the most striking: researchers found that people with lupus were 3.2 times more likely to develop lymphomas than the general population and 3.4 times more likely to develop non-Hodgkin's lymphoma, specifically. They also found that people with lupus were 1.7 times greater risk of developing leukemia.

"These results more precisely define cancer risk in SLE [than previous studies], highlighting a higher risk of hematological malignancies - both lymphoma and leukemia," says Sasha R. Bernatsky, MD, assistant professor in the Department of Medicine, Divisions of Rheumatology and Clinical Epidemiology, at McGill University, a medical scientist at the Research Institute of the McGill University Health Centre, and co-principle investigator in the ongoing study along with Ann E. Clarke, MD, and Rosalind Ramsey-Goldman, MD, Dr.PH. "However, the news may not be all that bad, considering that hematological cancers remain a rare event - one in every 1,250 patient-years of follow-up for these patients. Just what is driving the risk of cancer in SLE is still unknown, but we currently suspect that disease activity plays a role, although drug exposures have not been ruled out."

Study participants also demonstrated an increased likelihood of developing lung cancer (1.2 times as likely as the general population), cervical cancer (1.6 times more likely), vulvo-vaginal cancers (2.8 times more likely), and liver cancer (2. 2 times more likely). The study also shows that people with lupus who are younger than 40 have a particularly high risk, as they are 1.7 times more likely to develop cancer than the general population.

On the other hand, participants did display a significantly decreased risk of developing hormone-sensitive cancers, including breast cancer (0.7 times as likely as the general population), endometrial cancer (0.49 times the likelihood), and ovarian cancer (0.56 times the likelihood).

"The lower risk of several hormone-sensitive cancers may invoke the possibility of alterations in the metabolism from estrogen and/or other hormones," Dr. Bernatsky explains. "But, because female SLE patients may be at higher risk for cancers and pre-cancerous changes of the uterine cervix, they should try to undergo pap testing regularly once they become sexually active, especially if they take immunosuppressive drugs."

The American College of Rheumatology is an international professional medical society that represents more than 8,000 rheumatologists and rheumatology health professionals around the world. Its mission is to advance rheumatology. The ACR/ARHP Annual Scientific Meeting is the premier meeting in rheumatology. For more information about the meeting, visit www.rheumatology.org/education. Follow the meeting on twitter by using the official hashtag: #ACR2010.

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Editor's Notes: Dr. Bernatsky will present this research during the ACR Annual Scientific Meeting at the Georgia World Congress Center at 5:30 PM on Monday, November 8 in Room B 402. Dr. Bernatsky will be available for media questions and briefing at 8:30 AM on Tuesday, November 9 in the on-site press conference room, B 212.

Learn more about living well with rheumatic disease as well as rheumatologists and the role they play in health care.


Presentation Number: 731

Further Defining Cancer Risk in Systemic Lupus: Updated Results in an Expanded International Multi-Centre Cohort.

Sasha R. Bernatsky
(McGill UHC/RVH, Montreal, QC, Canada)

Ann E. Clarke
(Montreal General Hospital, Montreal, QC, Canada)

Michelle A. Petri
(Timonium, MD)

Murray B.Urowitz
(The Toronto Western Hospital, Toronto, ON, Canada)

Paul R. Fortin
(Toronto Western Hospital, Toronto, ON, Canada)

Dafna D. Gladman
(Toronto Western Hospital, Toronto, ON, Canada)

Sí¸ren Jacobsen
(Rigshospitalet - 4242, Copenhagen, Denmark)

Susan Manzi
(20West Penn Allegheny Health System, Pittsburgh, PA)

Graciela S. Alarcon
(Oakland, CA)

Ellen M. Ginzler
(SUNYDownstate Medical Center, Brooklyn, NY)

ChristineA. Peschken
(Univ of Manitoba, Winnipeg, MB, Canada)

Mary Anne Dooley
(Capital Health and Dalhousie University, Chapel Hill, NC)

John G. Hanly
(Queen Elizabeth II Health Services Center, Halifax, NS, Canada)

Ola Nived
(University Hospital, Lund, Sweden)

David Isenberg
(University College, London, UK)

Anisur Rahman
(University College, London, UK)

Gunnar K. Sturfelt
(17UCL Div of Medicine, Room 331, 3rd Floor, Lund, Sweden)

Jean-Luc Senecal
(Notre-Dame Hospital, M-4243, Montreal, QC, Canada)

Jeremy Labrecque
(McGill University, Montreal, Canada)

Elizabeth M. Turnbull
(McGill University Health Ctr, Montreal, QC, Canada)

Jennifer L. F. Lee
(RI McGill Univ Health Ctr, Montreal, QC, Canada)

Rosalind Ramsey-Goldman
(Northwestern University, Chicago, IL)

Purpose: Our previous collaborative effort demonstrated an association between systemic lupus (SLE) and cancer, driven primarily by lymphoma risk. We aimed to more precisely estimate cancer incidence rates in SLE, compared to the general population. We also present results stratified by age group.

Methods: We assembled an expanded multi-centre international cohort of clinically confirmed SLE patients. Patients at each center were linked to regional tumor registries to determine cancer occurrence. Standardized incidence ratios (SIRs) were calculated as the ratio of observed to expected cancers. Cancers expected were determined by multiplying person-years in the cohort by the geographically matched age, sex, and calendar year-specific cancer rates, and summing over all person-years.

Results: The 13,492 patients from 24 centers were observed for a total of 118,359 patient-years, with an average follow-up of 9 years. Within the observation interval, 632 cancers occurred. The data confirmed an increased risk of cancer among patients with SLE. For all cancers combined, the SIR estimate was 1.15 (95% confidence interval, 95% CI, 1.06-1.24), and for all hematologic malignancies combined, the SIR was 2.53 (95% CI 2.05-3.07). Regarding specific types of hematological malignancies, increased risk was demonstrated for all lymphomas (SIR 3.21, 95% CI 2.48-4.07) as well non-Hodgkin's lymphoma specifically (SIR 3.41, 95% CI 2.61-4.39), and for leukemia (1.69, 95% CI 1.00-2.67). We also demonstrated an increased risk of lung cancer (SIR 1.24; 95% CI 1.00-1.53), cervical cancer (SIR 1.65, 95% CI 1.09-2.41), vulvo-vaginal cancers (SIR 2.80, 95% CI 1.12-5.77), and hepatic cancer (SIR 2.18, 95% CI 1.16-3.73). Meanwhile, a significant decreased risk was seen for hormone-sensitive cancers, including breast cancer (SIR 0.70, 95% CI 0.58, 0.85), endometrial cancer (SIR 0.49, 95% CI 0.27, 0.83), and ovarian cancer (0.56, 95% CI 0.28, 0.97). When SIR estimates were stratified by age, SLE patients in the youngest age group (<40) appeared="" to="" have="" a="" particularly="" high="" relative="" cancer="" risk="" (compared="" to="" the="" general="" population),="" with="" an="" over-all="" cancer="" sir="" of="" 1.70="" (95%="" ci="" 1.34,="">

Conclusion: These results more precisely define cancer risk in SLE, highlighting a higher risk of hematological malignancies, both lymphoma and leukemia; these are being further studied in case-cohort analyses of drugs and disease activity. One additional hypothesis for the higher risk of certain events, such as cervical and vulvo-vaginal cancers, is the possibility of altered clearance of viruses (e.g. HPV). On the other hand, the lower risk of several hormone-sensitive cancers may invoke the possibility of alterations in the metabolism of estrogen and/or other hormones. Although cancers in general are more common with age, younger SLE patients have a particularly high relative cancer risk (compared to the general population).

Table: Cancer Risk in Systemic Lupus

Disclosure: Sasha Bernatsky, NIH: Research grants, The Arthritis Society of Canada: Research grants; Ann Clarke, NIH: Research grants, The Arthritis Society: Research grants; Michelle Petri, nothing to disclose; Murray Urowitz, nothing to disclose, Paul Fortin, nothing to disclose; Dafna Gladman, nothing to disclose; Sí¸ren Jacobsen, nothing to disclose; Susan Manzi, nothing to disclose; Graciela Alarcon, nothing to disclose; Ellen Ginzler, nothing to disclose; Christine Peschken, nothing to disclose; Mary Anne Dooley, nothing to disclose; John Hanly, nothing to disclose; Ola Nived, nothing to disclose; Gunnar Sturfelt, nothing to disclose; Jean-Luc Senecal, nothing to disclose; Jeremy Labrecque, nothing to disclose; Elizabeth Turnbull, nothing to disclose; Jennifer Lee, nothing to disclose; Rosalind Ramsey-Goldman, NIH: Research grants; David Isenberg: nothing to disclose; Anisur Rahman, nothing to disclose.

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